Human Skeletal Stem Cells Identified for the First Time

In 2015, researchers identified stem cells in rodents that only give rise to bone, cartilage or stromal cells – the cells in the spongy interior of bone – but the search for their human counterpart has proven fruitless until now.

It has taken more than ten years of research but finally scientists at Stanford University School of Medicine have made a breakthrough and have identified human skeletal stem cells in fetal and adult bones. Further, the researchers have derived skeletal stem cells from human induced pluripotent stem cells (IPSCs) that can be obtained from fat – The same fat that is removed through liposuction and usually discarded.

Skeletal stem cells are different from mesenchymal stem cells, which can differentiate into skeletal tissues as well as fat, connective tissue, and muscle cells. Mesenchymal stem cells can be obtained from various tissues, such as bone marrow, muscle, fat, and blood. While these stem cells have been used in various treatments to regenerate tissues, controlling the differentiation process is difficult as the cells respond to a wide range of signals that determine the cells that will be formed.

Skeletal stem cells on the other hand are tissue specific, and will only differentiate into bone, cartilage or stromal cells. That means that they would be much more useful for the treatment of degenerative, neoplastic, post-traumatic, and post-surgical skeletal disorders.

The discovery was made by the same team of researchers who identified skeletal stem cells in mice. For that discovery, the team used so-called rainbow mice – mice that had been genetically engineered so that different stem cells have different colors. This made it much easier to determine which stem cells differentiated into skeletal tissue.

The researchers were able to identify those stem cells, sequence the genes in those cells, and produce a genetic signature for skeletal stem cells. The same approach could not be used in humans, although the researchers were able to search for a similar genetic sequence in the growth plate of fetal bones obtained from aborted fetuses. Those cells were then differentiated into bone and cartilage in the lab.

The next stage of the research was to determine whether they had found the right stem cells. The researchers used freshly cut bone that had been removed during knee and hip replacement surgery, found the signature cells, and cultured them in the lab. As with the study on fetal bones, the researchers were able to generate new bone and cartilage in the lab.

Crucially, their efforts did not produce any other types of cells other than skeletal tissue, in contrast to efforts to grow skeletal tissue from mesenchymal stem cells. The researchers were also able to create skeletal stem cells from stromal cells obtained from liposuctioned fat.

“A half-million times a year, U.S. citizens have their fat sucked out and it’s discarded as medical waste,” said Michael Longaker, Deane P. and Louise Mitchell Professor, School of Medicine, Stanford University. “That’s a lot of material we could use to generate skeletal stem cells.” Though practical applications are still years away, he envisions these cells being used to replace damaged bone and joint tissue or treat degenerative skeletal diseases like osteoporosis.

What is not yet known is whether the researchers will be able isolate and extract sufficiently large numbers of the stem cells for them to prove to be clinically useful.

The research is detailed in the paper – Identification of the Human Skeletal Stem Cell – which was recently published in the Journal Cell. DOI: 10.1016/j.cell.2018.07.029